DELAYED CORONARY ENDOTHELIAL PROTECTION 24 HOURS AFTER PRECONDITIONING - ROLE OF FREE-RADICALS

Background Preconditioning (PC) induces delayed protection against myo cardial ischemia/reperfusion (I/R) injury. Whether a similar late prot ective effect exists in coronary endothelial cells is not known. Thus, we assessed whether PC also induces late protection against endotheli al injury after I/R and the potential role of reactive oxygen species as triggers for late PC in this setting.Methods and Results Rats were subjected to sham surgery or to PC with 1 cycle of 2 minutes I/5 minut es R and 2 cycles of 5 minutes I/5 minutes R in the absence or presenc e of the free radical scavenger N-2-mercaptopropionyl glycine (MPG). T wenty-four hours later, rats were subjected to 20 minutes I/60 minutes R in the absence or presence of MPG. At the end of R, coronary segmen ts (diameter, 200 to 300 mu m) were removed distal to the site of occl usion and mounted in wire myographs. I/R reduced the relaxations to ac etylcholine (maximal relaxations: sham, 72+/-6%; I/R, 31+/-6%), and th is impairment was prevented by MPG (64+/-7%), PC improved the response to acetylcholine (48+/-6%), but this beneficial effect was abolished by MPG (23+/-5%). Conclusions PC induces late protection against reper fusion-induced coronary endothelial injury. Moreover, in addition to b eing mediators of endothelial injury during reperfusion after prolonge d ischemia, reactive oxygen species produced during PC also protect th e coronary endothelium from reperfusion injury 24 hours later.